Chapter 139. Haemophilus Infections (Kỳ 3) Nontypable H. influenzae Nontypable H. influenzae is a common cause of community-acquired bacterial pneumonia in adults. Nontypable H. influenzae pneumonia is especially common among patients with COPD or AIDS. The clinical features of H. influenzae pneumonia are similar to those of other types of bacterial pneumonia (including pneumococcal pneumonia). Patients present with fever, cough, and purulent sputum, usually of several days' duration. Chest radiography reveals alveolar infiltrates in a patchy or lobar distribution. Gram-stained sputum contains a predominance of small, pleomorphic, coccobacillary gram-negative bacteria. Exacerbations of COPD caused by nontypable H. influenzae are characterized by increased cough, sputum production, and shortness of breath. Fever is low-grade, and no infiltrates are evident on chest x-ray. Nontypable H. influenzae is one of the three most common causes of childhood otitis media (the other two being Streptococcus pneumoniae and Moraxella catarrhalis) (Chap. 31). Infants are febrile and irritable, while older children report ear pain. Symptoms of viral upper respiratory infection often precede otitis media. The diagnosis is made by pneumatic otoscopy. An etiologic diagnosis, although not routinely sought, can be established by tympanocentesis and culture of middle-ear fluid. The increasing use of pneumococcal polysaccharide conjugate vaccines in infants is resulting in a relative increase in the proportion of otitis media cases that are caused by H. influenzae. Nontypable H. influenzae also causes puerperal sepsis and is an important cause of neonatal bacteremia. These nontypable strains, which are closely related to H. haemolyticus, tend to be of biotype IV and cause invasive disease after colonizing the female genital tract. Nontypable H. influenzae causes sinusitis (Chap. 31) in adults and children. In addition, the bacterium is a less common cause of various invasive infections that are reported primarily as small-series descriptions and case reports. These infections include empyema, adult epiglottitis, pericarditis, cellulitis, septic arthritis, osteomyelitis, endocarditis, cholecystitis, intraabdominal infections, urinary tract infections, mastoiditis, aortic graft infection, and bacteremia without a detectable focus. Diagnosis The most reliable method for establishing a diagnosis of Hib infection is recovery of the organism in culture. The CSF of a patient in whom meningitis is suspected should be subjected to Gram's staining and culture. The presence of gram-negative coccobacilli in Gram-stained CSF is strong evidence for Hib meningitis. Recovery of the organism from CSF confirms the diagnosis. Cultures of other normally sterile body fluids, such as blood, joint fluid, pleural fluid, pericardial fluid, and subdural effusion, are confirmatory in other infections. Detection of PRP is an important adjunct to culture in rapid diagnosis of Hib meningitis. Immunoelectrophoresis, latex agglutination, coagglutination, and enzyme-linked immunosorbent assay are effective in detecting PRP. These assays are particularly helpful when patients have received prior antimicrobial therapy and thus are especially likely to have negative cultures. Before the early 1980s, nontypable strains of H. influenzae were frequently misidentified as Hib because of their autoagglutination when serotypes were determined in agglutination assays. Since nontypable H. influenzae is primarily a mucosal pathogen, it is a component of a mixed flora; this situation makes etiologic diagnosis challenging. Nontypable H. influenzae infection is strongly suggested by the predominance of gram-negative coccobacilli among abundant polymorphonuclear leukocytes in a Gram-stained sputum specimen from a patient in whom pneumonia or tracheobronchitis is suspected. A sputum culture is helpful when interpreted along with the results of Gram's staining. Although bacteremia is detectable in a small proportion of patients with pneumonia due to nontypable H. influenzae, most such patients have negative blood cultures. A diagnosis of otitis media is based on the detection by pneumatic otoscopy of fluid in the middle ear. An etiologic diagnosis requires tympanocentesis but is not routinely sought. An invasive procedure is also required to determine the etiology of sinusitis; thus, treatment is often empirical once the diagnosis is suspected in light of clinical symptoms and sinus radiographs. Haemophilus Influenzae: Treatment Initial therapy for meningitis due to Hib should consist of a cephalosporin such as ceftriaxone or cefotaxime. For children, the dosage of ceftriaxone is 75– 100 mg/kg daily given in two doses 12 h apart. The pediatric dosage of cefotaxime is 200 mg/kg daily given in four doses 6 h apart. Adult dosages are 2 g every 12 h for ceftriaxone and 2 g every 4–6 h for cefotaxime. An alternative regimen for initial therapy is ampicillin (200–300 mg/kg daily in four divided doses) plus chloramphenicol (75–100 mg/kg daily in four divided doses). Therapy should continue for a total of 1–2 weeks. Administration of glucocorticoids to patients with Hib meningitis reduces the incidence of neurologic sequelae. The presumed mechanism is reduction of the inflammation induced by bacterial cell-wall mediators of inflammation when cells are killed by antimicrobial agents. Dexamethasone (0.6 mg/kg per day intravenously in four divided doses for 2 days) is recommended for the treatment of Hib meningitis in children >2 months of age. Invasive infections other than meningitis are treated with the same antimicrobial agents. For epiglottitis, the dosage of ceftriaxone is 50 mg/kg daily, and the dosage of cefotaxime is 150 mg/kg daily, given in three divided doses 8 h apart. Epiglottitis constitutes a medical emergency, and maintenance of an airway is critical. The duration of therapy is determined by the clinical response. A course of 1–2 weeks is usually appropriate. Many infections caused by nontypable strains of H. influenzae, such as otitis media, sinusitis, and exacerbations of COPD, can be treated with oral antimicrobial agents. Approximately 20–35% of nontypable strains produce β- lactamase (with the exact proportion depending on geographic location), and these strains are resistant to ampicillin. Several agents have excellent activity against nontypable H. influenzae, including amoxicillin/clavulanic acid, various extended- spectrum cephalosporins, the macrolides azithromycin and clarithromycin, and the new ketolide telithromycin. Fluoroquinolones are highly active against H. influenzae and are useful in adults with exacerbations of COPD. However, fluoroquinolones are not currently recommended for the treatment of children or pregnant women because of possible effects on articular cartilage. In addition to β-lactamase production, alteration of penicillin-binding proteins—a second mechanism of ampicillin resistance—has been detected in isolates of H. influenzae. Although rare in the United States, these β-lactamase- negative ampicillin-resistant strains are increasing in prevalence in Europe and Japan. Continued monitoring of the evolving antimicrobial susceptibility patterns of H. influenzae will be important. . Chapter 139. Haemophilus Infections (Kỳ 3) Nontypable H. influenzae Nontypable H. influenzae is a common cause. bacterium is a less common cause of various invasive infections that are reported primarily as small-series descriptions and case reports. These infections include empyema, adult epiglottitis, pericarditis,. cellulitis, septic arthritis, osteomyelitis, endocarditis, cholecystitis, intraabdominal infections, urinary tract infections, mastoiditis, aortic graft infection, and bacteremia without a detectable